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Source: Antiviral Research

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Total 49 results found since Jan 2013.

Targeted inhibition of Hantavirus replication and intracranial pathogenesis by a chimeric protein-delivered siRNA.
Abstract Hantavirus (HV) infection, which underlies hantavirus hemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome, remains to be a severe clinical challenge. Here, we synthesized small interfering RNAs (siRNAs) that target the encoding sequences of HV strain 76-118, and validated their inhibitory role in virus replication in HV-infected monkey kidney Vero E6 cells. A chimeric protein, 3G1-Cκ-tP, consisting of a single-chain antibody fragment (3G1) against the HV surface envelop glycoprotein, the constant region of human immunoglobulin κ chain (Cκ), and truncated protamine (amino acids 8-29,...
Source: Antiviral Research - October 7, 2017 Category: Virology Authors: Yang J, Sun JF, Wang TT, Guo XH, Wei JX, Jia LT, Yang AG Tags: Antiviral Res Source Type: research

Identification of KX2-391 as an inhibitor of HBV transcription by a recombinant HBV-based screening assay.
This study used recombinant HBV encoding NanoLuc to screen anti-HBV compounds from 1827 US Food and Drug Administration approved compounds and identified several compounds that suppressed HBV infection. Among them, KX2-391, a non-ATP-competitive inhibitor of SRC kinase and tubulin polymerization, was identified as a lead candidate for an anti-HBV drug. Treatment of sodium taurocholate cotransporting polypeptide (NTCP) transduced-HepG2 (HepG2-NTCP) or primary human hepatocytes with KX2-391 suppressed HBV replication in a dose-dependent manner. The anti-HBV activity of KX2-391 appeared not to depend on SRC kinase activity be...
Source: Antiviral Research - June 14, 2017 Category: Virology Authors: Harada K, Nishitsuji H, Ujino S, Shimotohno K Tags: Antiviral Res Source Type: research

Antiviral screen identifies EV71 inhibitors and reveals camptothecin-target, DNA topoisomerase 1 as a novel EV71 host factor.
Abstract Enterovirus 71 (EV71) is one of the causative agents of hand, foot and mouth disease (HFMD) associated with severe neurological disease. EV71's pathogenesis remains poorly understood and the lack of approved antiviral has led to its emergence as a clinically important neurotropic virus. The goals of this study were to: (i) identify novel anti-EV71 compounds that may serve as lead molecules for therapeutics; and (ii) investigate their targets in downstream studies. We screened a 502-compound library of highly purified natural products for anti-EV71 activities in a cell-based immunofluorescence assay that w...
Source: Antiviral Research - April 17, 2017 Category: Virology Authors: Wu KX, Chu JJ Tags: Antiviral Res Source Type: research

Identification of proximal biomarkers of PKC agonism and evaluation of their role in HIV reactivation.
CONCLUSION: Overall, our results offer new insights into the mechanism of action of PKC agonists, biomarkers of pathway engagement, and the potential role of EGR family in HIV reactivation. PMID: 27889530 [PubMed - as supplied by publisher]
Source: Antiviral Research - November 22, 2016 Category: Virology Authors: Vemula SV, Maxwell JW, Nefedov A, Wan BL, Steve J, Newhard W, Sanchez RI, Tellers D, Barnard RJ, Blair W, Hazuda D, Webber AL, Howell BJ Tags: Antiviral Res Source Type: research

Modelling Ebola virus dynamics: Implications for therapy.
Abstract Ebola virus (EBOV) causes a severe, often fatal Ebola virus disease (EVD), for which no approved antivirals exist. Recently, some promising anti-EBOV drugs, which are experimentally potent in animal models, have been developed. However, because the quantitative dynamics of EBOV replication in humans is uncertain, it remains unclear how much antiviral suppression of viral replication affects EVD outcome in patients. Here, we developed a novel mathematical model to quantitatively analyse human viral load data obtained during the 2000/01 Uganda EBOV outbreak and evaluated the effects of different antivirals....
Source: Antiviral Research - October 11, 2016 Category: Virology Authors: Martyushev A, Nakaoka S, Sato K, Noda T, Iwami S Tags: Antiviral Res Source Type: research

In vitro inhibition of African swine fever virus-topoisomerase II disrupts viral replication.
Abstract African swine fever virus (ASFV) is the etiological agent of a highly-contagious and fatal disease of domestic pigs, leading to serious socio-economic impact in affected countries. To date, neither a vaccine nor a selective anti-viral drug are available for prevention or treatment of African swine fever (ASF), emphasizing the need for more detailed studies at the role of ASFV proteins involved in viral DNA replication and transcription. Notably, ASFV encodes for a functional type II topoisomerase (ASFV-Topo II) and we recently showed that several fluoroquinolones (bacterial DNA topoisomerase inhibitors) f...
Source: Antiviral Research - August 24, 2016 Category: Virology Authors: Freitas FB, Frouco G, Martins C, Leitão A, Ferreira F Tags: Antiviral Res Source Type: research

Targeting the pseudorabies virus DNA polymerase processivity factor UL42 by RNA interference efficiently inhibits viral replication.
This study provides a new clue for the design of an intervention strategy against herpesviruses by targeting their processivity factors. PMID: 27387827 [PubMed - as supplied by publisher]
Source: Antiviral Research - July 3, 2016 Category: Virology Authors: Wang YP, Huang LP, Du WJ, Wei YW, Wu HL, Feng L, Liu CM Tags: Antiviral Res Source Type: research

Protein Phosphatase-1 Regulates Rift Valley Fever Virus Replication.
Abstract Rift Valley fever virus (RVFV), genus Phlebovirus family Bunyaviridae, is an arthropod-borne virus endemic throughout sub-Saharan Africa. Recent outbreaks have resulted in cyclic epidemics with an increasing geographic footprint, devastating both livestock and human populations. Despite being recognized as an emerging threat, relatively little is known about the virulence mechanisms and host interactions of RVFV. To date there are no FDA approved therapeutics or vaccines for RVF and there is an urgent need for their development. The Ser/Thr protein phosphatase 1 (PP1) has previously been shown to play a s...
Source: Antiviral Research - January 19, 2016 Category: Virology Authors: Baer A, Shafagati N, Benedict A, Ammosova T, Ivanov A, Hakami RM, Terasaki K, Makino S, Nekhai S, Kehn-Hall K Tags: Antiviral Res Source Type: research

Interleukin-24 inhibits influenza A virus replication in vitro through induction of toll-like receptor 3 dependent apoptosis.
This study demonstrates that IL-24 reduces the titer of different influenza A virus subtypes independently of type I interferon in an apoptosis dependent manner. The anti-viral effect of IL-24 correlated with caspase-3 activation and could be blocked by a pan-caspase inhibitor and by small interfering RNA (siRNA) directed towards TLR3. Surprisingly, caspase-3 activation in influenza A virus/IL-24-stimulated cells correlated with the down-regulation of the B-cell lymphoma 2 (Bcl-2) family member myeloid cell leukemia 1 (Mcl-1). Correspondingly, knockdown of Mcl-1 by siRNA enhanced caspase activation in influenza A virus inf...
Source: Antiviral Research - September 11, 2015 Category: Virology Authors: Weiss R, Laengle J, Sachet M, Shurygina AP, Kiselev O, Egorov A, Bergmann M Tags: Antiviral Res Source Type: research

Small interfering RNAs targeting peste des petits ruminants virus M mRNA increase virus-mediated fusogenicity and inhibit viral replication in vitro.
In this study, three different small interfering RNAs (siRNA) were designed on the basis of translated region for PPRV Nigeria 75/1M mRNA, and were subsequently synthesized for their transfection into Vero-SLAM cells, followed by infection with PPRVs. The results showed that two out of three siRNAs robustly induced cell-to-cell fusion as early as 36h post-infection with PPRVs, effectively suppressed expression of the M protein by interference for the M mRNA, and eventually inhibited viral replication in vitro. These findings led us to speculate that siRNA-mediated knockdown of the M protein would alter its interaction with...
Source: Antiviral Research - August 25, 2015 Category: Virology Authors: Liu F, Wu X, Zou Y, Li L, Liu S, Chi T, Wang Z Tags: Antiviral Res Source Type: research

Enhanced Suppression of Adenovirus Replication by Triple Combination of Anti-Adenoviral siRNAs, Soluble Adenovirus Receptor Trap sCAR-Fc and Cidofovir.
Abstract Adenoviruses (Ad) generally induce mild self-limiting respiratory or intestinal infections but can also cause serious disease with fatal outcomes in immunosuppressed patients. Antiviral drug therapy is an important treatment for adenoviral infections but its efficiency is limited. Recently, we have shown that gene silencing by RNA interference (RNAi) is a promising new approach to inhibit adenoviral infection. In the present in vitro study, we examined whether the efficiency of an RNAi-based anti-adenoviral therapy can be further increased by combination with a virus receptor trap sCAR-Fc and with the ant...
Source: Antiviral Research - May 27, 2015 Category: Virology Authors: Pozzuto T, Röger C, Kurreck J, Fechner H Tags: Antiviral Res Source Type: research

Expression of a single siRNA against a conserved region of NP gene strongly inhibits in vitro replication of different Influenza A virus strains of avian and swine origin.
In conclusion, these findings reveal new siRNA sequences able to inhibit Influenza A virus replication and provide a basis for the development of siRNAs as prophylaxis and therapy for influenza infection both in humans and animals. PMID: 25986248 [PubMed - as supplied by publisher]
Source: Antiviral Research - May 16, 2015 Category: Virology Authors: Stoppani E, Bassi I, Dotti S, Lizier M, Ferrari M, Lucchini F Tags: Antiviral Res Source Type: research

Kinome siRNA screen identifies novel cell-type specific dengue host target genes.
Abstract Dengue is a global emerging infectious disease, with no specific treatment available. To identify novel human host cell targets important for dengue virus infection and replication, an image-based high-throughput siRNA assay screening of a human kinome siRNA library was conducted using human hepatocyte cell line Huh7 infected with a recent dengue serotype 2 virus isolate BR DEN2 01-01. In the primary siRNA screening of 779 kinase-related genes, knockdown of 22 genes showed a reduction in DENV-2 infection. Conversely, knockdown of 8 genes enhanced viral infection. To assess host cell specificity, the confi...
Source: Antiviral Research - July 18, 2014 Category: Virology Authors: Kwon YJ, Heo J, Wong HE, Cruz DJ, Velumani S, da Silva CT, Mosimann AL, Duarte Dos Santos CN, Freitas-Junior LH, Fink K Tags: Antiviral Res Source Type: research

Chikungunya virus nsP3 & nsP4 interacts with HSP-90 to promote virus replication: HSP-90 inhibitors reduce CHIKV infection and inflammation in vivo.
In this study, using biochemical pull-downs, mass-spectrometry, and microscopic imaging techniques, we have identified novel interactions between CHIKV nsP3 or nsP4 proteins with the host stress-pathway chaperone HSP-90 protein. Indeed, silencing of HSP-90 transcripts using siRNA disrupts CHIKV replication in cultured cells. Furthermore, drugs targeting HSP-90, such as commercially available geldanamycin, as well as other specific HSP-90 inhibitor drugs that had been obtained from a purinome mining approach (HS-10 and SNX-2112) showed dramatic reduction in viral titers and reduced inflammation in a CHIKV mouse model of sev...
Source: Antiviral Research - December 31, 2013 Category: Virology Authors: Rathore AP, Haystead T, Das PK, Merits A, Ng ML, Vasudevan SG Tags: Antiviral Res Source Type: research

Nuclear Import and Export Inhibitors Alter Capsid Protein Distribution in Mammalian Cells and Reduce Venezuelan Equine Encephalitis Virus Replication.
Abstract Targeting host responses to invading viruses has been the focus of recent antiviral research. Venezuelan Equine Encephalitis Virus (VEEV) is able to modulate host transcription and block nuclear trafficking at least partially due to its capsid protein forming a complex with the host proteins importin α/β1 and CRM1. We hypothesized that disrupting the interaction of capsid with importin α/β1 or the interaction of capsid with CRM1 would alter capsid localization, thereby lowering viral titers in vitro. siRNA mediated knockdown of importin α, importin β1, and CRM1 altered capsid localization, confirmin...
Source: Antiviral Research - October 22, 2013 Category: Virology Authors: Lundberg L, Pinkham C, Baer A, Amaya M, Narayanan A, Wagstaff KM, Jans DA, Kehn-Hall K Tags: Antiviral Res Source Type: research